WO2011043272A1 - LIGAND POUR CATALYSEUR DE SYNTHÈSE ASYMÉTRIQUE ET PROCÉDÉ POUR LA PRODUCTION D'UN COMPOSÉ CYCLIQUE α-ALCÉNYLIQUE L'UTILISANT - Google Patents
LIGAND POUR CATALYSEUR DE SYNTHÈSE ASYMÉTRIQUE ET PROCÉDÉ POUR LA PRODUCTION D'UN COMPOSÉ CYCLIQUE α-ALCÉNYLIQUE L'UTILISANT Download PDFInfo
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- WO2011043272A1 WO2011043272A1 PCT/JP2010/067279 JP2010067279W WO2011043272A1 WO 2011043272 A1 WO2011043272 A1 WO 2011043272A1 JP 2010067279 W JP2010067279 W JP 2010067279W WO 2011043272 A1 WO2011043272 A1 WO 2011043272A1
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- ligand
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- alkenyl
- experimental example
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- 239000003446 ligand Substances 0.000 title claims abstract description 97
- 239000003054 catalyst Substances 0.000 title claims abstract description 42
- 238000011914 asymmetric synthesis Methods 0.000 title claims abstract description 27
- 238000004519 manufacturing process Methods 0.000 title claims description 32
- 150000001923 cyclic compounds Chemical class 0.000 title claims description 7
- 238000000034 method Methods 0.000 title abstract description 15
- 230000008569 process Effects 0.000 title abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 55
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 claims description 38
- 239000012018 catalyst precursor Substances 0.000 claims description 30
- 150000001298 alcohols Chemical class 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 125000001033 ether group Chemical group 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 150000004808 allyl alcohols Chemical class 0.000 claims description 15
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical group CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 150000004292 cyclic ethers Chemical class 0.000 claims description 8
- 239000007810 chemical reaction solvent Substances 0.000 claims description 6
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000000962 organic group Chemical group 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 239000007858 starting material Substances 0.000 description 44
- -1 polycyclic ethers Chemical class 0.000 description 33
- 239000000243 solution Substances 0.000 description 31
- 235000019441 ethanol Nutrition 0.000 description 30
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
- 125000001309 chloro group Chemical group Cl* 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 238000006297 dehydration reaction Methods 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 238000007363 ring formation reaction Methods 0.000 description 14
- 229910052799 carbon Inorganic materials 0.000 description 13
- 230000018044 dehydration Effects 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000013543 active substance Substances 0.000 description 8
- 125000004430 oxygen atom Chemical group O* 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000012046 mixed solvent Substances 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 0 *c1ccc(cccc2)c2c1-c1nc(*)ccc1* Chemical compound *c1ccc(cccc2)c2c1-c1nc(*)ccc1* 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- JISUFFORTXEXSG-UHFFFAOYSA-N 2-(2-chloronaphthalen-1-yl)-3-methylpyridine Chemical compound CC1=CC=CN=C1C1=C(Cl)C=CC2=CC=CC=C12 JISUFFORTXEXSG-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011949 solid catalyst Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- ASNHGEVAWNWCRQ-UHFFFAOYSA-N 4-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound OCC1(O)COC(O)C1O ASNHGEVAWNWCRQ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000007872 degassing Methods 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- GMHRXXGPLXKTCN-HNQUOIGGSA-N (e)-6-hydroxyhex-4-enoic acid Chemical compound OC\C=C\CCC(O)=O GMHRXXGPLXKTCN-HNQUOIGGSA-N 0.000 description 1
- GILWSHCPFILQDX-UHFFFAOYSA-N 2-(2-chloronaphthalen-1-yl)-5-methyl-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC(C)=CC=C1C1=C(Cl)C=CC2=CC=CC=C12 GILWSHCPFILQDX-UHFFFAOYSA-N 0.000 description 1
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- MKZMEJAKGAQMRL-UHFFFAOYSA-N 3-methyl-2-(2-methylnaphthalen-1-yl)pyridine Chemical compound CC1=CC=CN=C1C1=C(C)C=CC2=CC=CC=C12 MKZMEJAKGAQMRL-UHFFFAOYSA-N 0.000 description 1
- HLARMRKNRAJIQW-UHFFFAOYSA-N 3-methyl-2-(2-phenylnaphthalen-1-yl)pyridine Chemical compound CC1=CC=CN=C1C1=C(C=2C=CC=CC=2)C=CC2=CC=CC=C12 HLARMRKNRAJIQW-UHFFFAOYSA-N 0.000 description 1
- NUZVHQQEGICDQB-UHFFFAOYSA-N 5-ethenyloxolan-2-one Chemical compound C=CC1CCC(=O)O1 NUZVHQQEGICDQB-UHFFFAOYSA-N 0.000 description 1
- LOIDSLPQWMONFC-UHFFFAOYSA-N 6-(2-chloronaphthalen-1-yl)-5-methylpyridine-2-carbonitrile Chemical compound CC1=CC=C(C#N)N=C1C1=C(Cl)C=CC2=CC=CC=C12 LOIDSLPQWMONFC-UHFFFAOYSA-N 0.000 description 1
- ZYNPQZMTIADJGA-UHFFFAOYSA-N 6-(2-chloronaphthalen-1-yl)-5-methylpyridine-2-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)N=C1C1=C(Cl)C=CC2=CC=CC=C12 ZYNPQZMTIADJGA-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- PTDQAGORQFYXOX-UHFFFAOYSA-N C(C1)C2C3=C1C23 Chemical compound C(C1)C2C3=C1C23 PTDQAGORQFYXOX-UHFFFAOYSA-N 0.000 description 1
- QPUZVUFOYDZTHN-UHFFFAOYSA-N C1(=CC=CC=C1)C1=C(C2=CC=CC=C2C=C1)C1=CC=CC(=N1)C#N Chemical compound C1(=CC=CC=C1)C1=C(C2=CC=CC=C2C=C1)C1=CC=CC(=N1)C#N QPUZVUFOYDZTHN-UHFFFAOYSA-N 0.000 description 1
- YFTHPAKWQBTOLK-SSDOTTSWSA-N C=C[C@H]1OCCCC1 Chemical compound C=C[C@H]1OCCCC1 YFTHPAKWQBTOLK-SSDOTTSWSA-N 0.000 description 1
- IXQGCWUGDFDQMF-UHFFFAOYSA-N CCc(cccc1)c1O Chemical compound CCc(cccc1)c1O IXQGCWUGDFDQMF-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 238000006130 Horner-Wadsworth-Emmons olefination reaction Methods 0.000 description 1
- 238000000023 Kugelrohr distillation Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000001361 allenes Chemical class 0.000 description 1
- 238000005937 allylation reaction Methods 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- KCBQNBQGPQUGSD-HWKANZROSA-N n-[(e)-6-hydroxyhex-4-enyl]-4-methylbenzenesulfonamide Chemical compound CC1=CC=C(S(=O)(=O)NCCC\C=C\CO)C=C1 KCBQNBQGPQUGSD-HWKANZROSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- ROTONRWJLXYJBD-UHFFFAOYSA-N oxan-2-ylmethanol Chemical compound OCC1CCCCO1 ROTONRWJLXYJBD-UHFFFAOYSA-N 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical group [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2217—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
- B01J31/2243—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/06—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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Definitions
- the present invention relates to a ligand for asymmetric synthesis catalyst and a method for producing ⁇ -alkenyl cyclic compounds using the same. More specifically, the present invention relates to a ligand having a specific structure, easily coordinated to Ru contained in the catalyst precursor, and useful for the production of chiral ⁇ -alkenyl cyclic compounds, and these catalyst precursors. The present invention relates to a method for producing ⁇ -alkenyl cyclic compounds in which a specific allyl alcohol is subjected to a dehydration cyclization reaction in the presence of a catalyst comprising a ligand for an asymmetric synthesis catalyst.
- optically active substances having an asymmetric carbon atom among physiologically active substances there are many optically active substances having an asymmetric carbon atom among physiologically active substances, and it is important to obtain an optically active substance having a predetermined steric structure.
- Examples of a method for obtaining this optically active substance include a method of synthesizing a racemate and then fractionating an optically active substance having a predetermined steric structure by optical resolution or the like.
- this method is low in efficiency because chemical conversion is necessary. For this reason, research and development of asymmetric synthesis methods capable of selectively synthesizing optically active substances having a predetermined steric structure are in progress.
- One of the most important structural units in optically active substances such as polycyclic ethers includes cyclic ethers having an asymmetric center (for example, see Non-Patent Document 1). Of the many basic structures reported so far, ⁇ -alkenyl substituted cyclic ethers are known to be most useful. Further, with regard to this ⁇ -alkenyl-substituted cyclic ether, a catalyst having particularly high selectivity has attracted attention.
- Wacker-type oxidized cyclization of orthoallyl or homoallylphenol derivatives see, for example, Non-Patent Document 2
- ⁇ -hydroxyallyl ⁇ -Trost type intramolecular allylation using esters for example, see Non-Patent Document 3
- addition of alcohols to alkynes for example, see Non-Patent Document 4
- addition of alcohols to allenes A synthesis method such as (see, for example, Non-Patent Document 5) is known.
- the present invention provides a ligand having a specific structure, easily coordinated to Ru of a catalyst precursor, and useful for the production of chiral ⁇ -alkenyl cyclic compounds, and asymmetric synthesis with these catalyst precursors
- An object of the present invention is to provide a method for producing an ⁇ -alkenyl cyclic compound in which a specific allyl alcohol is subjected to a dehydration cyclization reaction in the presence of a catalyst comprising a catalyst ligand.
- the present invention is as follows.
- R 1 is —Cl or —Br
- R 2 is —CH 3 or —CF 3
- R 3 is —CH 2 —CH ⁇ CH 2 or —H.
- the R 1 is —Cl and the R 2 is —CH 3, which is represented by the formula (1) or the formula (2);
- the allyl alcohol is the ⁇ -hydroxyallyl alcohol
- the cyclic compound is a cyclic ether having a 5-membered ring ether structure or a 6-membered ring ether structure.
- the ⁇ -hydroxyallyl alcohol represented by the formula (6) is a compound of the following (a) to (l): A process for producing an ⁇ -alkenyl cyclic compound as described in 1. above. (A); R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —H, and R 5 is —H.
- R 6 in the formula (6) is —CH 2 CH 2 —, R 4 is —H, and R 5 is —H.
- C R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —CH 3 , and R 5 is —H.
- D R 6 in the formula (6) is —CH 2 CH 2 —, R 4 is —CH 3 , and R 5 is —H.
- E R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —C 2 H 5 , and R 5 is —H.
- R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —nC 5 H 11 , and R 5 is —H.
- G R 6 in the above formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —CH 2 (iC 3 H 7 ), and R 5 is —H.
- H R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —H, and R 5 is —CH 3.
- R 6 in the formula (6) is —C (CH 3 ) 2 CH 2 CH 2 —, R 4 is —H, and R 5 is —H.
- HO—R 6 in the formula (6) is represented by the following formula (7), R 4 is —CH 3 , and R 5 is —H.
- K HO—R 6 in the formula (6) is represented by the following formula (8), R 4 is —H, and R 5 is —CH 3.
- Bn is a benzyl group (C 6 H 5 CH 2 —).
- L HO—R 6 in the formula (6) is represented by the following formula (9), R 4 is —CH 3 , and R 5 is —H. 6).
- the ratio 3 (M 1 / M 2 ) of the number of moles (M 1 ) of the ⁇ -hydroxyallyl alcohols to the number of moles (M 2 ) of the ligand for asymmetric synthesis catalyst is 100 to 1000 .
- To 5. The method for producing an ⁇ -alkenyl cyclic compound according to any one of the above. 7). 2. The temperature of the reaction is 80 to 120 ° C. To 6. The method for producing an ⁇ -alkenyl cyclic compound according to any one of the above. 8). 2. The reaction solvent is dimethylacetamide. To 7. The method for producing an ⁇ -alkenyl cyclic compound according to any one of the above.
- the ligand for an asymmetric synthesis catalyst of the present invention easily coordinates to Ru of a catalyst precursor having a specific structure to form an asymmetric synthesis catalyst, and this catalyst dehydrates specific allyl alcohols. Cyclization can be carried out to produce chiral ⁇ -alkenyl cyclic compounds with high yield and high enantioselectivity. In the case where R 1 is —Cl and R 2 is —CH 3 and is represented by the formula (1) or (2), the chiral ⁇ can be obtained with higher yield and higher selectivity. -Alkenyl cyclic compounds can be prepared.
- ⁇ -alkenyl cyclic compounds of the present invention many kinds of allyl alcohols are subjected to a dehydration cyclization reaction with simple operations and steps, and a chiral ⁇ with high yield and high enantioselectivity. -Alkenyl cyclic compounds can be easily produced.
- the allyl alcohol is ⁇ -hydroxyallyl alcohol and the cyclic compound is a cyclic ether having a 5-membered ring ether structure or a 6-membered ring ether structure
- many kinds of ⁇ -hydroxyallyl alcohols are used.
- reaction temperature is 80 to 120 ° C.
- ⁇ -alkenyl cyclic compounds can be efficiently produced with high yield and selectivity without requiring a long time for the reaction.
- the reaction solvent is dimethylacetamide, a stable reaction is possible, and ⁇ -alkenyl cyclic compounds can be efficiently produced with high yield and selectivity.
- 1 is a 1 H-NMR spectrum of allyl 6- (2-chloronaphthalen-1-yl) -5-methylpyridine-2-carboxylate.
- FIG. 6 is a 13 C-NMR spectrum of allyl 6- (2-chloronaphthalen-1-yl) -5-methylpyridine-2-carboxylate.
- 1 is a 1 H-NMR spectrum of an ⁇ -alkenyl cyclic ether produced using a compound represented by the above formula (a) as ⁇ -hydroxyallyl alcohol.
- 3 is a 13 C-NMR spectrum of an ⁇ -alkenyl cyclic ether produced using a compound represented by the formula (a) as ⁇ -hydroxyallyl alcohols.
- Ligand for asymmetric synthesis catalyst of the present invention (hereinafter sometimes simply referred to as ligand) is one of the above formulas (1) to (4). It is represented by one.
- R 1 is —Cl (chlorine atom) and Any of -Br (bromine atom) may be used, but -Cl is preferred.
- R 2 may be either —CH 3 (methyl group) or —CF 3 , but is preferably —CH 3 .
- R 3 may be either —CH 2 —CH ⁇ CH 2 (allyl group) or —H (hydrogen atom), but is preferably —CH 2 —CH ⁇ CH 2 . That is, an allyl ester type ligand is preferable to an acid type. Therefore, the ligand is preferably an allyl ester type ligand in which R 1 is —Cl and R 2 is —CH 3 in the formulas (1) and (2).
- R 1 is —Cl.
- R 2 is preferably —CH 3
- R 3 is preferably —CH 2 —CH ⁇ CH 2 . That is, an allyl ester type ligand is preferable to an acid type. Accordingly, in the formulas (3) and (4), an allyl ester type ligand in which R 1 is —Cl and R 2 is —CH 3 is preferable.
- the ligand for an asymmetric synthesis catalyst of the present invention is a catalyst precursor represented by the above formula (5), that is, [Ru (C 5 H 5 ) (CH 3 CN) 3 ] PF 6 [the following formula ( 10), which has a structural portion in which three acetonitriles (CH 3 CN) are coordinated to Ru. ]
- the ligand and catalyst precursor of the present invention may be used by adding a solvent to a solid ligand and a solid catalyst precursor and mixing them, or a ligand dissolved in a solvent and a solid catalyst precursor.
- each solvent may be the same and may differ.
- the prepared ligand may be isolated once and used by dissolving in a solvent at the time of use, or may be used as manufactured, that is, as dissolved in the solvent used at the time of manufacture. [In the formula (10), the broken line between Ru and N represents a coordination bond. ]
- allyl alcohol is an ⁇ -hydroxyallyl alcohol represented by the formula (6)
- an ⁇ -alkenyl cyclic ether having a 5-membered ring ether structure or a 6-membered ring ether structure can be produced. it can.
- R 4 may be either —H or an alkyl group having 1 to 5 carbon atoms, —H It is preferable that When R 4 is an alkyl group, the number of carbon atoms may be 1 to 5, but is preferably —CH 3 having 1 carbon atom or —C 2 H 5 (ethyl group) having 2 carbon atoms, In particular, —CH 3 having 1 carbon atom is more preferable. Furthermore, this alkyl group may be either a linear alkyl group or a branched alkyl group. R 5 may be either —H or —CH 3 , but is preferably —H.
- R 6 is a divalent organic group in which the oxygen atom of the hydroxyl group at the ⁇ -position is bonded to the carbon atom to which R 5 is bonded to form a 5-membered ether structure or a 6-membered ether structure. It is.
- the ⁇ -hydroxyallyl alcohols used as starting materials are ⁇ -alkenyl cyclic ethers having R 4 , R 5 and R 6 as described above and having a 5-membered ring ether structure or a 6-membered ring ether structure.
- the starting material is not particularly limited as long as it can be obtained, and various starting materials can be used.
- R 6 in the formula (6) is —CH 2 CH 2 —, —CH 2 CH 2
- the structural portion represented by CH 2 — or —C (CH 3 ) 2 CH 2 CH 2 — and HO—R 6 in the formula (6) are represented by the formula (7), the formula (8) or the formula (9 ⁇ -hydroxyallyl alcohols, which are structural moieties represented by
- allyl alcohols Meldrum's acid type allyl alcohols, sulfonylaminoallyl alcohols and carboxyallyl alcohols can also be used.
- ⁇ -hydroxyallyl alcohols the intramolecular dehydration cyclization reaction of the starting material
- ⁇ -alkenyl cyclic compounds can be produced.
- the hydrogen atom of the substituent reacts with the hydroxyl group, and ⁇ -alkenyl cyclic compounds are formed by dehydration cyclization.
- the substituent has a hydrogen atom, an oxygen atom, and a carbon atom, and the hydrogen atom that participates in the dehydration reaction is bonded to the carbon atom.
- intramolecular dehydration cyclization reaction is promoted in a reaction system using the ligand for asymmetric synthesis catalyst of the present invention and a specific catalyst precursor, and ⁇ -alkenyl cyclic compounds Can be manufactured efficiently.
- what is bonded to the carbon atom of the skeleton part excluding the substituent may be a hydrogen atom or an alkyl group.
- the substituent has a hydrogen atom, a nitrogen atom, a sulfur atom, and an oxygen atom, and the hydrogen atom that participates in the dehydration reaction is bonded to the nitrogen atom.
- intramolecular dehydration cyclization reaction is promoted in a reaction system using the ligand for asymmetric synthesis catalyst of the present invention and a specific catalyst precursor, and ⁇ -alkenyl cyclic compounds Can be manufactured efficiently.
- what is bonded to the carbon atom of the skeleton part excluding the substituent may be a hydrogen atom or an alkyl group.
- the substituent has a hydrogen atom, an oxygen atom, and a carbon atom, and the hydrogen atom that participates in the dehydration reaction is bonded to the oxygen atom.
- intramolecular dehydration cyclization reaction is promoted in a reaction system using the ligand for asymmetric synthesis catalyst of the present invention and a specific catalyst precursor, and ⁇ -alkenyl cyclic compounds Can be manufactured efficiently.
- what is bonded to the carbon atom of the skeleton part excluding the substituent may be a hydrogen atom or an alkyl group.
- an asymmetric synthesis catalyst ligand and a catalyst precursor are mixed to form an asymmetric synthesis catalyst, and then reacted with a blended starting material.
- ⁇ -alkenyl cyclic compounds are produced.
- the method for mixing the ligand and the catalyst precursor is not particularly limited as described above, but a method in which a solution in which the ligand is dissolved is added to and mixed with the solid catalyst precursor charged into the reactor is preferable.
- the starting material is produced as a liquid or solid stereoisomer, and is dissolved in an appropriate solvent when used. Further, the solution in which the starting material is dissolved is blended with the solution in which the catalyst system is formed by the ligand and the catalyst precursor, and ⁇ -alkenyl cyclic compounds are generated.
- the solvent for dissolving the ligand and the solvent for dissolving the catalyst precursor may be the same or different as described above, but the solvent for dissolving the starting material is also the catalyst. It may be the same as or different from at least one of the solvent for dissolving the precursor and the solvent for dissolving the ligand.
- the solvent include dimethylacetamide (DMA), dimethylformamide (DMF), tetrahydrofuran (THF), cyclopentyl methyl ether (CPME), dioxane, dichloromethane, acetone, toluene, methyl alcohol, ethyl alcohol, t-butyl alcohol, Examples include i-propyl alcohol, acetic acid, water and the like.
- solvents for dissolving the catalyst precursor and the ligand are preferable as solvents for dissolving the catalyst precursor and the ligand, respectively.
- a solvent for dissolving the starting material usually a solvent serving as a reaction solvent, DMA, DMF, THF, CPME, t-butyl alcohol and the like are preferable, and DMA is more preferable.
- the ratio (M 1 / M 2 ) of the number of moles of starting material (M 1 ) to the number of moles of ligand (M 2 ) can produce the desired ⁇ -alkenyl cyclic compounds.
- the ratio is preferably 90% or more, particularly 95% or more, and more preferably 99% or more, practically, although the conversion rate from the starting material to ⁇ -alkenyl cyclic compounds is not particularly limited.
- the ratio (M 1 / M 2 ) is preferably 50 to 5000, particularly 70 to 3000, and more preferably 100 to 1000.
- the conversion can be sufficiently increased with a very small amount of catalyst as compared with the conventional method.
- the reaction conditions are not particularly limited, and the reaction conditions depend on the type of the ligand and the starting material, particularly the type of the starting material, etc. It is preferable to adjust appropriately.
- the reaction temperature depends on the reaction time, but from a practical point of view, it is preferably 50 to 150 ° C., particularly 70 to 130 ° C., more preferably 80 to 120 ° C.
- the reaction time can be 0.1 to 3 hours, particularly 0.1 to 1.5 hours when the reaction temperature is 80 to 120 ° C.
- the reaction temperature is a low temperature of less than 80 ° C., By making the reaction time longer, the conversion rate from the starting material to the ⁇ -alkenyl cyclic compounds can be sufficiently increased to 99% or more.
- the atmosphere during the reaction is an inert atmosphere, and this inert atmosphere is not particularly limited.
- the atmosphere can be a nitrogen gas atmosphere or a rare gas atmosphere such as argon gas, helium gas, or neon gas.
- a conventionally known method such as distillation, adsorption, extraction, recrystallization, or a combination of these methods is used.
- the desired ⁇ -alkenyl cyclic compounds can be recovered and purified.
- the target optically active substance can be further purified by optical resolution or the like, if necessary.
- a mechanism in which an ⁇ -alkenyl cyclic compound is formed by forming a catalyst system using a ligand and a catalyst precursor, and mixing and reacting with a specific allyl alcohol is, for example,
- allyl alcohol is ⁇ -hydroxyallyl alcohol, it is considered as follows.
- (R) -Cl-Naph-PyCOOH [acid type ligand of formula (1)] is complexed with [CpRu (CH 3 CN) 3 ] PF 6 (catalyst precursor) to form [CpRu ((R ) -Cl-Naph-PyCOOH)] PF 6 to capture the allyl alcohol substrate, resulting in a sub / cat complex (starting material / catalyst complex) [see formula (11) below].
- the electrophilicity of the ⁇ carbon is remarkably improved by the hydrogen bond between the proton of the carboxylic acid of the ligand and the hydroxy group of the ⁇ -hydroxyallyl alcohol.
- the ⁇ -allyl complex (R, R Ru ) -Asyn, anti [see the following formula (12)] (syn is the positional relationship between the ⁇ -allyl 2-position proton and the 3-position substituent, and anti is the carboxylate ligand and the ⁇ -allyl 3-position substituent.
- the (R) -Naph-PyCOOH / CpRu catalyst gives an S product in preference to the inside attack capable of hydrogen bonding between the oxygen atom of the carboxylate ligand and the ⁇ -hydroxy proton.
- the S body is generated by the outside attack via the (R, S Ru ) Asyn, syn diastereomer.
- there are two diastereomeric intermediates such as steric repulsion between the Cp, ⁇ allyl, and PyCOO moieties on the Ru atom, hydrogen bonding between CpH / Cl, and CH- ⁇ interaction between benzene rings / CpH.
- Example 1 [Preparation of allyl 6- (2-chloronaphthalen-1-yl) -5-methylpyridine-2-carboxylate]
- 2- (2-chloronaphthalen-1-yl) -3-methylpyridine To a dried Schlenk tube with a capacity of 250 mL, 2- (2-triethylsilyl) naphthalen-1-yl) -3-methyl 8 g (24 mmol) of pyridine and 48 mL of dichloromethane were added, and the temperature was lowered to ⁇ 78 ° C.
- this oily substance was purified by silica gel column chromatography (100 g, the solvent was hexane and ethyl acetate in a mass ratio of 5: 1), and 856 mg (yield 93%) of 6- (2-chloronaphthalen-1-yl) was obtained. ) -5-methylpyridine-2-carbonitrile was obtained.
- optical purity of each enantiomer separated was determined by high performance liquid chromatography [column: CHIRALCEL OD-H (manufactured by DAICEL, ⁇ 0.46 cm ⁇ 25 cm), solvent: hexane and 2-propanol at a mass ratio of 5: 1. Mixed solvent, flow rate: 1 mL / min, wavelength of light source: 254 nm] [(R) -isomer peaked at 14.1 min, (S) -isomer peaked at 25.0 min. It was. ].
- a ligand in which —Cl is replaced with a phenyl group includes 3-methyl-2- (2-phenylnaphthalen-1-yl) pyridine and 5-methyl- Prepared by a synthesis method via 6- (2-phenylnaphthalen-1-yl) pyridine-2-carbonitrile. Further, the racemate of each ligand was separated into (R) -form and (S) -form by high performance liquid chromatography as in the case of the ligand of the present invention.
- Example 2 [Production of ⁇ -alkenyl cyclic ethers] (Experimental Examples 1 to 3) 4.34 mg (10.0 ⁇ mol) of the catalyst precursor represented by the formula (5) was charged into a 50-mL Schlenk tube with a Young valve, which was dried and filled with Ar, and a magnetic stir bar was added.
- the ligand prepared in Example 1 [as shown in Table 1, the acid form of Formula (1) (Experimental Example 1) and the acid form of Formula (2) (Experimental Example 2), and the formula (1) Allyl ester type (Experimental Example 3)] 1.00 mL (10.0 mM dichloromethane solution was used. Therefore, the amount of ligand was 10.0 ⁇ mol) was added by an airtight syringe.
- Compound (a) which is ⁇ -hydroxyallyl alcohol used as a starting material for producing ⁇ -alkenyl cyclic ethers, was prepared as follows. Synthesis by a conventionally known method of Horner-Wadsworth-Emmons transformation between the 2nd and 3rd carbons using the corresponding ⁇ , ⁇ -unsaturated esters, followed by DIBAL-H transformation did. Stereoisomers were separated by silica gel column chromatography at the stage of ⁇ , ⁇ -unsaturated esters. Compounds (b) to (l) ⁇ -hydroxyallyl alcohols used as starting materials in Example 4 to be described later, and compounds as comparative examples in which R 6 has one more methylene group than compound (a) was produced in the same manner.
- Example 3 (Experimental Examples 4 to 22) In Example 2, various conditions were changed as shown in Table 1 to produce an ⁇ -alkenyl cyclic ether represented by the formula (14).
- Experimental Example 4 The same as Experimental Example 3, except that the starting material concentration was 1000 mM and the ligand concentration was 10 mM.
- Experimental Example 5 The same as Experimental Example 3, except that the ligand concentration was 0.1 mM, that is, the catalyst amount was 1/10.
- Experimental Example 6 The same as Experimental Example 3, except that the starting material concentration was 1000 mM, that is, the starting material amount was increased 10 times and the ligand was an allyl ester type of the formula (2).
- Experimental Example 7 The same as Experimental Example 3, except that the reaction temperature was 50 ° C.
- Experimental Example 8 The same as Experimental Example 3 except that the solvent was DMF.
- Experimental Example 9 The same as Experimental Example 3, except that the solvent was CH 3 CN.
- Experimental Example 10 The same as Experimental Example 3, except that the solvent was acetone.
- Experimental Example 11 The same as Experimental Example 3, except that the solvent was THF.
- Experimental Example 12 The same as Experimental Example 3, except that the solvent was CPME.
- Experimental Example 13 The same as Experimental Example 3 except that the solvent was dioxane.
- Experimental Example 14 The same as Experimental Example 3, except that the solvent was CH 2 Cl 2 .
- Experimental Example 15 The same as Experimental Example 3, except that the solvent was toluene.
- Experimental Example 16 The same as Experimental Example 3 except that the solvent was tC 4 H 9 OH.
- Experimental Example 17 The same as Experimental Example 16, except that the starting material concentration was 1000 mM, that is, the starting material amount was 10 times.
- Experimental Example 18 The same as Experimental Example 3, except that the solvent was iC 3 H 7 OH.
- Experimental Example 19 The same as Experimental Example 3, except that the solvent was C 2 H 5 OH.
- Experimental Example 20 The same as Experimental Example 3, except that the solvent was CH 3 OH.
- Experimental Example 21 The same as Experimental Example 3, except that the solvent was H 2 O.
- Experimental Example 22 The same as Experimental Example 3, except that the solvent was CH 3 COOH.
- the conversion and enantioselectivity in Experimental Examples 4 to 22 were determined in the same manner as described above. The results of Example 2 and Example 3 are also shown in Table 1.
- Experimental Example 23 which was reacted in the same manner as Experimental Example 3, except that a ligand in which —Cl was replaced with —CH 3 in the allyl ester type of the formula (1), was used. 23, except that the ligand concentration of 0.1 mM was used in Experimental Example 24 and the allyl ester type of the formula (1) was replaced with a ligand in which —Cl was replaced with a phenyl group. The reacted ⁇ -alkenyl cyclic ether of Experimental Example 25 was produced. Further, the conversion rates in Experimental Examples 23 to 25 and the enantioselectivity in Experimental Example 23 were determined in the same manner as described above. The production conditions and results of Experimental Examples 23 to 25 are shown in Table 1.
- Example 1 using the acid form of the formula (1) as the ligand and DMA as the solvent, and the experiment using the acid type of the formula (2) as the ligand and DMA as the solvent
- the conversion is 99% or more
- er is 97: 3 or 3:97, indicating that both the conversion and the selectivity are high.
- Experimental Example 3 using the allyl ester type of the formula (1)
- Experimental Example 4 using the starting material and the ligand having a 10-fold concentration in Experimental Example 3, and in Experimental Example 3, the catalyst amount was reduced to 1/10.
- the ligand was an allyl ester type of the formula (2), the catalyst amount was kept as it was and the starting material was 10 times the amount. Has been obtained.
- Experimental Example 25 in which the reaction was carried out in the same manner as Experimental Example 3, except that a ligand in which —Cl was replaced with a phenyl group in the allyl ester type of the formula (1) was used, Experimental Example 3 as well as Experimental Example 3 It can be seen that the conversion is even lower than 23, and that a ligand in which —Cl is replaced with a phenyl group cannot be put to practical use.
- Example 4 (Production of various ⁇ -alkenyl cyclic ethers using various starting materials) As shown in Table 2, using the compounds (a) to (l), the corresponding ⁇ -alkenyl cyclic ether represented by the formula (14) and the experiments represented by the following formulas (15) to (25) The ⁇ -alkenyl cyclic ethers of Examples 26-37 were prepared. The reaction was carried out under the same conditions as in Example 2 except for the following points: the starting material was 100 mM, the ligand was 1 mM, the solvent was DMA, the reaction temperature was 100 ° C., and the reaction time was 1 hour. It carried out in.
- the difference from the standard conditions is (1) The concentration of the starting material was 1000 mM in Experimental Example 26 using the compound (a). (2) The reaction time was 3 hours in Experimental Example 32 using the compound (g). (3) In Experimental Example 33 using the compound (h), the reaction temperature was 70 ° C., and the reaction time was 10 hours. (4) In Experimental Examples 35 to 37 using compounds (j) to (l), the solvent was a mixed solvent of t-C 4 H 9 OH and DMA having a mass ratio of 10: 1. (5) In Experimental Example 36, the reaction time was set to 24 hours after the above (5). It is. The enantioselectivity (er) in Experimental Examples 26 to 37 was determined in the same manner as described above.
- the isolated yield was determined by partitioning the reaction solution with 3 mL of a mixed solvent of pentane and ether (3: 1 by mass) and 5 mL of water, filtering the organic layer with silica gel, and then at 0 ° C. and 50 mmHg. The product was isolated and weighed (except for experimental examples 27 and 29). The results are also shown in Table 2.
- Bn is a benzyl group (C 6 H 5 CH 2 —).
- Example 5 Corresponding ⁇ -alkenyl cyclic compounds were prepared using various allyl alcohols having different substituents.
- Experimental Example 39 (Dehydrative cyclization reaction of Meldrum's acid type allyl alcohol) In a reaction tube equipped with a Young valve having a capacity of 20 mL, a 300 ⁇ L (333 mM concentration solution) of a dichloromethane solution of 2- (E) -5-hydroxypent-3-en-1-ylmeldrum acid as a starting material was used under an argon stream. Therefore, the amount of starting material is 100 ⁇ mol). The solution was concentrated under reduced pressure, and 1.00 mL of dichloromethane was added, followed by freeze degassing three times.
- the enantiomeric ratio was also determined by gas chromatographic analysis of the product [column; CHIRALDEX B-PM (0.25 mm ⁇ 0.125 ⁇ m ⁇ 30 m), temperature; 100 ° C., split ratio; 100: 1]. As a result, the ratio of the integrated values of the respective peaks was 83:17.
- the amount of the ligand was 10.0 ⁇ mol) was added.
- the solution was then carefully concentrated under reduced pressure and brought to atmospheric pressure with argon.
- the starting material solution prepared as described above was then added using a cannula and stirred in an oil bath at 100 ° C. After 20 minutes, the reaction mixture was subjected to silica gel column chromatography (sample; 30 g, developing solvent; ether) to isolate 4-ethenylbutyrolactone. Thereafter, Kugelrohr distillation (35 ° C., 0.01 mmHg) was performed to obtain a colorless oil (75.6 mg, addition rate: 70%).
- the enantiomeric ratio was also determined by gas chromatography analysis of the product [column; CHIRALDEX B-PM (0.25 mm ⁇ 0.125 ⁇ m ⁇ 30 m), temperature: held at 40 ° C. for 5 minutes, heating rate 1 ° C./min, Hold at 65 ° C. for 65 minutes, split ratio; 100: 1].
- the ratio of the integrated values of each peak was 99: 1.
- the present invention is not limited to the description of the above-described embodiment, and various modifications can be made within the scope of the present invention according to the purpose, application, and the like.
- the ligand and the catalyst precursor are mixed and then the starting material is blended and reacted.
- the ligand, the catalyst precursor, and the starting material are simultaneously mixed with an appropriate reaction solvent. It is also possible to produce ⁇ -alkenyl cyclic compounds by dissolving them in Further, a solution in which a ligand and a catalyst precursor are dissolved can be blended and reacted with a solution in which a starting material is dissolved.
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- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
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US13/499,404 US8822696B2 (en) | 2009-10-07 | 2010-10-01 | Ligand for asymmetric synthesis catalyst, and process for production of alpha-alkenyl cyclic compound using the same |
JP2011535371A JP5692812B2 (ja) | 2009-10-07 | 2010-10-01 | 不斉合成触媒用配位子及びそれを用いたα−アルケニル環状化合物の製造方法 |
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Citations (5)
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WO2002016249A1 (fr) * | 2000-08-24 | 2002-02-28 | Mitsubishi Denki Kabushiki Kaisha | Filin en fibre synthetique pour ascenseurs |
WO2002038628A2 (fr) * | 2000-11-07 | 2002-05-16 | Symyx Technologies, Inc. | Ligands de pyridylamine substitues, complexes, catalyseurs et procedes pour la polymerisation, et polymeres |
EP1308450A2 (fr) * | 2001-11-06 | 2003-05-07 | Symyx Technologies, Inc. | Complexes d' amines et pyridyl substitués par titanium, catalyseurs et procédé de polymérisation d'éthylène et de styrène |
WO2007129664A1 (fr) * | 2006-05-02 | 2007-11-15 | National University Corporation Nagoya University | Ligand tétradentate chiral pour catalyse asymétrique et applications |
WO2008085655A1 (fr) * | 2007-01-08 | 2008-07-17 | Exxonmobil Chemical Patents Inc. | Procédés d'oligomérisation d'oléfines avec des catalyseurs à base de chrome, pyrine, mono-oxazoline |
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AR037228A1 (es) * | 2001-07-30 | 2004-11-03 | Dow Agrosciences Llc | Compuestos del acido 6-(aril o heteroaril)-4-aminopicolinico, composicion herbicida que los comprende y metodo para controlar vegetacion no deseada |
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2010
- 2010-10-01 WO PCT/JP2010/067279 patent/WO2011043272A1/fr active Application Filing
- 2010-10-01 US US13/499,404 patent/US8822696B2/en not_active Expired - Fee Related
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Patent Citations (5)
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WO2002016249A1 (fr) * | 2000-08-24 | 2002-02-28 | Mitsubishi Denki Kabushiki Kaisha | Filin en fibre synthetique pour ascenseurs |
WO2002038628A2 (fr) * | 2000-11-07 | 2002-05-16 | Symyx Technologies, Inc. | Ligands de pyridylamine substitues, complexes, catalyseurs et procedes pour la polymerisation, et polymeres |
EP1308450A2 (fr) * | 2001-11-06 | 2003-05-07 | Symyx Technologies, Inc. | Complexes d' amines et pyridyl substitués par titanium, catalyseurs et procédé de polymérisation d'éthylène et de styrène |
WO2007129664A1 (fr) * | 2006-05-02 | 2007-11-15 | National University Corporation Nagoya University | Ligand tétradentate chiral pour catalyse asymétrique et applications |
WO2008085655A1 (fr) * | 2007-01-08 | 2008-07-17 | Exxonmobil Chemical Patents Inc. | Procédés d'oligomérisation d'oléfines avec des catalyseurs à base de chrome, pyrine, mono-oxazoline |
Non-Patent Citations (3)
Title |
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OHLOFF G. ET AL: "Preparation of tetrahydropyran and tetrahydrofuran derivatives from 1,7- and 1,6-allyl-diols, resp., by dehydration in the allyl position", HELVETICA CHIMICA ACTA, vol. 47, no. 2, 1964, pages 602 - 626 * |
TANAKA S. ET AL: "Asymmetric Dehydrative Cyclization of omega-Hydroxy Allyl Alcohols Catalyzed by Ruthenium Complexes", ANGEWANDTE CHEMIE, INTERNATIONAL EDITION, vol. 48, no. 47, 9 November 2009 (2009-11-09), pages 8948 - 8951 * |
TOMOAKI SEKI ET AL.: "omega-Hydroxy Allyl Alcohol-Rui no Shokubaiteki Fuseikanka", ANNUAL MEETING OF UNION OF CHEMISTRY-RELATED SOCIETIES IN CHUBU AREA, JAPAN YOKOSHU, vol. 40, 7 November 2009 (2009-11-07), pages 177 * |
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US20120220780A1 (en) | 2012-08-30 |
JP5692812B2 (ja) | 2015-04-01 |
US8822696B2 (en) | 2014-09-02 |
JPWO2011043272A1 (ja) | 2013-03-04 |
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